The long term objective of this project is to elucidate the molecular events which underlie secretion-dependent aggregation of human platelets. The immediate goal of the experiments proposed here are to clarify the role of the endogenous platelet lectin (which is the glycoprotein, thrombospondin) in the secretion-dependent aggregation of platelets (thrombospondin is secreted from alpha-granules). This goal will be attained by using a combination of biochemical, chemical and immunological techniques to identify those regions (each composed only of a contiguous sequence of amino acids) of thrombospondin (the endogenous platelet lectin) which play a critical role(s) in platelet aggregation. This work should result in the synthesis of short peptides (each composed of a contiguous sequence of amino acids found in thrombospondin) which can be used as tools for elucidating the molecular details of secretion-dependent aggregation of platelets. These peptides may also be capable of controlling "irreversible" platelet aggregation. Thus, these peptides may provide a rationale for designing peptides that have prophylactic and/or therapeutic value for patients with thrombotic tendencies.